For the past two years, the May 16-31 edition of Express Pharma has been a GMP Special issue, highlighting topics crucial to quality in pharma manufacturing. Our first GPM Special issue dated May 16-31, 2016 asked a very pertinent question: Are we grappling skewed perceptions of GMPs? (https://issuu.com/indianexpressgroup/docs/ep-20160531pages) With the visual of five blind men trying to identify different non compliance issues related to data integrity, lab controls, etc, the edition made the point that quality issues were like the ‘elephant in the room’: too big to miss, yet most pharma companies were in denial and tackled these aspects in silos. A line up of global experts gave their perceptions on this vexing topic. With global regulators making it clear that senior managements would be held accountable for lapses in quality, we hoped that the ‘elephant in the boardroom’ has been finally acknowledged and addressed.
We took forward this theme in our May 16-31, 2017 GMP Special issue (https://issuu.com/indianexpressgroup/
docs/ep-20170531pages) in which we focussed on the upskilling initiatives of pharma companies in India, as a way to prepare their employees to follow GMPs, data integrity protocols, etc. Hopefully, such initiatives will see a reduction in warning letters and import recalls, though it will take a few more years to see the results of these initiatives.
This year, we decided to explore how GMPs can and should be implemented as early as possible in the formulation research and development (fR&D) lifecycle. Regulators are asking for more details and documentation of early phase development, to check for GMP deficiencies between the development and scale up phases. Sources relate how ANDAs that do not contain evidence of development of products in accordance with the principles of QbD could face a Refusal to Receive (RTR) action or a Complete Response Letter that is equivalent to a WL for failure of the site to adhere to GMP issues. This calls for a new approach, where an integrated quality team will review dossiers before submission to identify any gaps in GMPs between development and scale up.
Pharma companies have also realised the hard way that what goes in, comes out. In other words, if they use low quality inputs (raw materials, active pharmaceutical ingredients (APIs), excipients and other constituents of the final medicine), in a poorly designed and controlled production process, the output is hardly likely to be of high quality. The result? Increased chances of batch failures and non-compliance.
What if we could anticipate and solve these issues in the initial phases of fR&D? Besides drug design and testing the potency of API and finding the best drug delivery platform, for novel or generic formulations, this stage also involves the selection of ingredient and excipient manufacturers for the final formulation. With pharma supply chains spanning continents, the lack of consistency in quality of these excipients poses a huge problem. Poor quality or inconsistent characteristics of even one ingredient could adversely impact patient safety. Hence, the excipient industry has evolved a system of independent third party audits and certifications to separate the wheat from the chaff.
The idea is that rather than test for substandard products at the final stages, why not control the quality in the early stages to prevent creation of substandard products? This approach improves efficiency of the formulation and manufacturing workflows as well as shortens development times.
Early stage testing may seem logical but pharma companies traditionally tested only the finished final product, or designated testing to the later part of the production process. By this stage, it was too late to make changes and save the batch. And worse, late stage quality testing merely detected poor quality product but did nothing to detect the case of the failure or prevent future non compliance. Due diligence at this stage, both from supplier as well as pharma companies, can nip most issues in the bud. (Read how companies are coping with these issues in the cover story of the May 16-31, issue: Never too early for QbD)
Industry observers also point out that the CDSCO and DCGI’s office are facilitating workshops, through various industry associations like IDMA, to help pharma companies in India to evolve from Schedule M to WHO GMP compliance. A gap analysis in August /September 2015 identified the gaps in GMPs in Schedule M and WHO GMP, and today many companies are reportedly working on these issues.
Just as pharma companies in India are evolving from Schedule M to WHO GMP compliance on the GMP front, there is an urgent need for a similar evolution in serialisation and traceability for pharmaceuticals exported from India. While the Directorate General of Foreign Trade (DGFT) has been working for several years to implement this system, industry observers point out that a failed and under-resourced implementation could jeopardise India’s reputation within the global pharma industry. Technical challenges, such as product numbering that does not align with global standards, are preventing the distribution of product and this will definitely impact patient access. Security problems, such as requirements to load ‘dummy’ or fake serial number data into the government database, only expand the risk of counterfeiting. While DGFT has announced a six-month suspension of the requirements, if these problems are not addressed in that time frame, India’s reputation as a global leader will be significantly damaged. Just as we seem to have a plan to plug the GMP gaps, we need a similar strategy on serialisation and traceability. One that will allow pharma companies in India to be in harmony with global norms. Hopefully, that is next on the agenda.